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000178288 1001_ $$0P:(DE-HGF)0$$aRoig-Merino, Alicia$$b0$$eFirst author
000178288 245__ $$aAn episomal DNA vector platform for the persistent genetic modification of pluripotent stem cells and their differentiated progeny.
000178288 260__ $$a[New York, NY]$$bElsevier$$c2022
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000178288 520__ $$aThe genetic modification of stem cells (SCs) is typically achieved using integrating vectors, whose potential integrative genotoxicity and propensity for epigenetic silencing during differentiation limit their application. The genetic modification of cells should provide sustainable levels of transgene expression, without compromising the viability of a cell or its progeny. We developed nonviral, nonintegrating, and autonomously replicating minimally sized DNA nanovectors to persistently genetically modify SCs and their differentiated progeny without causing any molecular or genetic damage. These DNA vectors are capable of efficiently modifying murine and human pluripotent SCs with minimal impact and without differentiation-mediated transgene silencing or vector loss. We demonstrate that these vectors remain episomal and provide robust and sustained transgene expression during self-renewal and targeted differentiation of SCs both in vitro and in vivo through embryogenesis and differentiation into adult tissues, without damaging their phenotypic characteristics.
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000178288 650_7 $$2Other$$aDNA vector
000178288 650_7 $$2Other$$aSMAR
000178288 650_7 $$2Other$$adifferentiation
000178288 650_7 $$2Other$$aembryonic stem cell
000178288 650_7 $$2Other$$aepisome
000178288 650_7 $$2Other$$ainduced pluripotent stem cell
000178288 650_7 $$2Other$$anonintegrative
000178288 650_7 $$2Other$$areprogramming
000178288 650_7 $$2Other$$aself-renewal
000178288 650_7 $$2Other$$atransgenesis
000178288 7001_ $$0P:(DE-He78)157a1fcb274700b6427b980f8f4b3e9f$$aUrban, Manuela$$b1$$eFirst author$$udkfz
000178288 7001_ $$0P:(DE-He78)3391c5ad790ea5359189d11f073fb103$$aBozza, Matthias$$b2$$udkfz
000178288 7001_ $$0P:(DE-He78)d60847f8be80aa39abf7a3cdeff75bdf$$aPeterson, Julia D$$b3$$udkfz
000178288 7001_ $$aBullen, Louise$$b4
000178288 7001_ $$0P:(DE-He78)df5fc2e4d9ec0b232d0adf43cd6bc7b5$$aBüchler-Schäff, Marleen$$b5$$udkfz
000178288 7001_ $$0P:(DE-He78)382c3025ef63551628ccc5bc5e702034$$aStäble, Sina$$b6$$udkfz
000178288 7001_ $$0P:(DE-He78)db41d10e17712fc21628c50a14f4d507$$avan der Hoeven, Franciscus$$b7$$udkfz
000178288 7001_ $$0P:(DE-He78)799d978330dff449f8244947929a4518$$aMüller-Decker, Karin$$b8$$udkfz
000178288 7001_ $$aMcKay, Tristan R$$b9
000178288 7001_ $$0P:(DE-He78)7b613cadb8c16ce178713e15b85d982c$$aMilsom, Michael D$$b10$$udkfz
000178288 7001_ $$0P:(DE-He78)15dff5647002b4dcfe892b251cd14b62$$aHarbottle, Richard$$b11$$eLast author$$udkfz
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